The methods disclosed herein relate to rodent models of human disease. Specifically, the described and claimed subject matter relate to methods of characterizing potential therapeutics for efficacy for use in treating, preventing, or ameliorating pathological conditions associated with specific mental symptoms such as dementia, depression, or apathy using a method of scoring behavior-related symptoms in a rodent model.
Numerous physical disorders produce behavioral or mental symptoms such as dementia, anxiety, apathy, depression, and personality changes. Alzheimer's disease (AD), the most common neurodegenerative disorder and cause of senile dementia, is the target of intense clinical and basic research efforts as there is presently neither a predictor or cure. In addition to cognitive deficits, AD patients experience “behavioral and psychological symptoms of dementia” (BPSD), including, sleep disturbances, paranoia, aggression, and anxiety. These symptoms often manifest before cognitive deficits are apparent and cause significant distress both to patients and caregivers (Buhr & White, 2007. J Amer Med Dir Assoc 8:e101-113; Buhr & White 2006. J Amer Med Dir Assoc 7:180-192).
Efforts have been made to develop animal models which exhibit the pathophysiological hallmarks of the disease, such extracellular β-amyloid-rich plaques and intraneuronal neurofibrillary tangles (NFTs); however, behavioral correlates between mouse and man are difficult. Attempts to characterize behavioral deficits in these models include tests of curiosity and apathy (Boissier's hole-board test), lack of ability to cope with mild stressors (white-black box), and increased emotionality (freezing behavior). These studies have provided some insight into the behavioral manifestations of these models; however, conducting behavioral tests requires specialized equipment and training, and can be very labor intensive. Therefore, an easily identifiable behavioral marker of disease in an animal model is desired by those skilled in the art.